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Báo cáo khoa học: "On the epidemiology of influenza: reply to Radonovich et al"

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Virology Journal BioMed Central Open Access Commentary On the epidemiology of influenza: reply to Radonovich et al John J Cannell*1, Michael Zasloff2, Cedric F Garland3, Robert Scragg4 and Edward Giovannucci5 Address: 1Department of Psychiatry, Atascadero State Hospital, 10333 El Camino Real, Atascadero, CA 93423, USA, 2Departments of Surgery and Pediatrics, Georgetown University, Washington, DC, USA, 3Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA, 4Department of Epidemiology and Biostatistics, University of Auckland, Auckland, New Zealand and 5Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA Email: John J Cannell* - jcannell@ash.dmh.ca.gov; Michael Zasloff - maz5@georgetown.edu; Cedric F Garland - cgarland@earthlink.net; Robert Scragg - r.scragg@auckland.ac.nz; Edward Giovannucci - egiovann@hsph.harvard.edu * Corresponding author Published: 11 August 2009 Received: 24 June 2009 Accepted: 11 August 2009 Virology Journal 2009, 6:121 doi:10.1186/1743-422X-6-121 This article is available from: http://www.virologyj.com/content/6/1/121 © 2009 Cannell et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract On the epidemiology of influenza: reply to Radonovich LJ, Martinello RA, Hodgson M, Milton DK, Nardell EA. Influenza and ultraviolet germicidal irradiation. Virol J. 2008, 5:149 tion. They take factual issue with our theory that the Commentary To the Editor: ultraviolet C radiation (UVC) lamps, used in the past to sterilize the upper air in some VA hospitals, may have We thank Radonovich et al [1] for commenting on our exerted some, or most, of their effects – not by sanitizing paper [2], in which we attempted to use the epidemiology air – but by increasing 25(OH)D levels. of vitamin D to clarify the manifold mysteries surround- ing the epidemiology of influenza. Since our publication, Radonovich et al assert there was no patient exposure Ginde et al [3] have produced additional evidence in sup- from UVC germicidal lamps, as they were installed to irra- port of our theories. They studied the relationship diate only the upper air and never shone directly on between 25-hydroxy-vitamin D [25(OH)D] levels and patients, thus "minimizing UV exposure in the occupied recent upper respiratory tract infections (URI) in 18,883 space below." Careful inspection of such an arrangement, participants in the Third National Health and Nutrition in a 1957 Baltimore VA hospital, is illuminating [5]. Pho- Examination. Compared to individuals with serum 25- tographs show lights that seemed to shine indirectly on hydroxy-vitamin D levels of > 30 ng/ml, those with levels patients, apparently 24 hours per day, seven days a week. < 10 ng/ml had 55% higher odds of a recent URI. Further- Depending on the characteristics of the reflective surfaces, more, very recent evidence indicates 25(OH)D levels of it seems possible – even likely from the photographs – even 30 ng/ml often signify chronic substrate starvation that a small amount of UVC was reflected downward [4], thus the full antimicrobial properties of vitamin D toward the patients. may be understated. Radonovich et al then assert that even if some UVC Radonovich et al did not supply any evidence against the reflected downward, it could not produce Vitamin D, as main hypotheses proposed in our paper, only to a specu- UVC radiation does not do so, citing MacLaughlin et al lation we made about ultraviolet germicidal air irradia- [6]. The belief that UVC radiation cannot produce vitamin Page 1 of 3 (page number not for citation purposes)
Virology Journal 2009, 6:121 http://www.virologyj.com/content/6/1/121 D may be a widespread misconception. Fortunately for centage made of the surface is significant, studies of cuta- humans, as UVC is highly carcinogenic, UVC does not neous Vitamin D production in modern humans, unless penetrate the atmosphere and certainly does not trigger unwashed, will not give accurate estimates of Vitamin D cutaneous Vitamin D during the course of normal human production in early man and thus an estimate of the "nat- affairs. However, closer reading of their MacLaughlin et al ural" 25(OH)D levels present when the human genome reference [6] would have revealed that significant photo- evolved. synthesis of vitamin D from 7-dehydrohydrocholesterol (7-DHC) occurs at UVC wavelengths in the epidermal lip- We repeat our aside hypothesis that the patients in UVC ids the authors extracted [as illustrated in MacLaughlin et irradiated hospitals may have been the beneficiaries of al's figure 1(B)]. Indeed, per photon, UVC photosynthesis more than just cleaner air. Much more importantly, influ- is greater than UVB [as illustrated in MacLaughlin et al's enza is just one of many seasonal infections sensitive to figure 1(C)]. the broad spectrum anti-microbial peptides (AMP) that vitamin D up-regulates [2]. Invasive pneumococcal dis- Furthermore, several animal studies indicate that UVC, ease, meningococcal disease, and group A streptococcal which should never be used in man, is highly effective in disease are all highly seasonal [12-14] and all are sensitive both producing vitamin D and in treating rachitic rats [7]. to AMP [15-17]. Would vitamin D be an effective adjuvant Knudson and Benford studied numerous UV wavelengths in these devastating diseases? in rats, finding UVC as effective as any of the UVB wave- lengths studied in curing rickets [8]. If all human Vitamin As research into vitamin D's remarkable effects on innate D production is intra-epidermal, the academic question immunity quickens [18], we hope to see the day when appears to be, how deep does UVC penetrate human epi- infectious disease experts use all available antimicrobial dermis? Campbell et al found evidence that significant strategies, including testing the serum 25(OH)D level in amounts of UVC penetrate through the stratum corneum, all patients with severe infections. In our opinion, physi- stratum lucidum, stratum granulosum, and small cians treating such patients should vigorously replete amounts of UVC even reach the upper layers of the 7- them, quickly achieving 25(OH)D levels in the high range DHC-rich stratum spinosum [9]. Thus, UVC penetrates far of normal. enough into the epidermis to trigger some intra-epider- mal vitamin D production. Again, because UVC is so References mutagenic, we are heartened to find no studies that 1. Radonovich LJ, Martinello RA, Hodgson M, Milton DK, Nardell EA: Influenza and ultraviolet germicidal irradiation. Virol J 2008, directly test this theory in living humans. 5:149. 2. Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E: On the epidemiology of influenza. Virol J 2008, 5:29. However, even if no UVC penetrated the stratum cor- 3. Ginde AA, Mansbach JM, Camargo CA Jr: Association between neum, Helmer and Jensen published a remarkable serum 25-hydroxyvitamin D level and upper respiratory human/animal study in 1937, showing that significant tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med 2009, 169(4):384-390. amounts of Vitamin D are made on the surface of human 4. Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW: 25- skin [10]. They collected surface oils from young men, Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Am J Clin Nutr 2008, irradiated the oils, and showed those oils rapidly cured 87(6):1738-1742. rachitic rats. Then, they tested a very practical and impor- 5. Riley RL, Wells WF, Mills CC, Nyka W, Mclean RL: Air hygiene in tant question, can those oils be removed by washing. tuberculosis: quantitative studies of infectivity and control in a pilot ward. Am Rev Tuberc 1957, 75:420-431. Indeed they found a simple water wash removed much of 6. MacLaughlin JA, Anderson RR, Holick MF: Spectral character of the Vitamin D from the surface of human skin. Holick et sunlight modulates photosynthesis of previtamin D3 and its al's landmark study showing most human Vitamin D pro- photoisomers in human skin. Science 1982, 216(4549):1001-1003. duction occurs in the deep epidermis was based on surgi- 7. Bunker JWM, Harris RS, Mosher LM: Relative efficiency of active cally obtained (and assumedly surgically prepped) skin wave-lengths of ultraviolet in activation of 7-dehydrocholes- terol. J Am Chem Soc 1940, 62(3):508-511. samples that then had surface oils removed again by 8. Knudson A, Benford F: Quantitative studies of the effectiveness washing in hot water [11]. Indeed, to accurately address of ultraviolet radiation of various wavelengths in rickets. J the question, one would need to obtain unwashed human Biol Chem 1938, 124:287-299. 9. Campbell C, Quinn AG, Angus B, Farr PM, Rees JL: Wavelength skin, difficult to do even from cadavers. specific patterns of p53 induction in human skin following exposure to UV radiation. Cancer Res 1993, 53(12):2697-2699. It appears to us that the percentage of Vitamin D made on 10. Helmer AC, Jensen CH: Vitamin D precursors removed from the skin by washing. Studies Inst Divi Thomae 1937, 1:207-216. the surface of the human epidermis, compared to that 11. Holick MF, MacLaughlin JA, Clark MB, Holick SA, Potts JT Jr, Ander- made inta-epidermally, is unknown at this time and in son RR, Blank IH, Parrish JA, Elias P: Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science need of additional and careful research. What percentage 1980, 210(4466):203-205. of the Vitamin D made in human skin after sun exposure 12. Dowell SF, Whitney CG, Wright C, Rose CE Jr, Schuchat A: Sea- is removed by simply washing? Furthermore, as the per- sonal patterns of invasive pneumococcal disease. Emerg Infect Dis 2003, 9(5):573-9. Page 2 of 3 (page number not for citation purposes)
Virology Journal 2009, 6:121 http://www.virologyj.com/content/6/1/121 13. Jensen ES, Lundbye-Christensen S, Pedersen L, Sørensen HT, Schøn- heyder HC: Seasonal variation in meningococcal disease in Denmark: relation to age and meningococcal phenotype. Scand J Infect Dis 2003, 35(4):226-9. 14. Vlaminckx BJ, van Pelt W, Schouls LM, van Silfhout A, Mascini EM, Elzenaar CP, Fernandes T, Bosman A, Schellekens JF: Long-term surveillance of invasive group A streptococcal disease in The Netherlands, 1994–2003. Clin Microbiol Infect 2005, 11(3):226-231. 15. Lee HY, Andalibi A, Webster P, Moon SK, Teufert K, Kang SH, Li JD, Nagura M, Ganz T, Lim DJ: Antimicrobial activity of innate immune molecules against Streptococcus pneumoniae, Moraxella catarrhalis and nontypeable Haemophilus influen- zae. BMC Infect Dis 2004, 4:12. 16. Bergman P, Johansson L, Wan H, Jones A, Gallo RL, Gudmundsson GH, Hökfelt T, Jonsson AB, Agerberth B: Induction of the antimi- crobial peptide CRAMP in the blood-brain barrier and meninges after meningococcal infection. Infect Immun 2006, 74(12):6982-6991. 17. Ryan MA, Akinbi HT, Serrano AG, Perez-Gil J, Wu H, McCormack FX, Weaver TE: Antimicrobial activity of native and synthetic surfactant protein B peptides. J Immunol 2006, 176(1):416-425. 18. White JH: Vitamin D signaling, infectious diseases, and regu- lation of innate immunity. Infect Immun 2008, 76(9):3837-3843. Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime." Sir Paul Nurse, Cancer Research UK Your research papers will be: available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 3 of 3 (page number not for citation purposes)

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